Devices and methods for treating maxillary sinus disease

ABSTRACT

Devices and methods are described for improving drainage and/or aeration of maxillary sinuses and for treating maxillary sinus disease. Spacer devices are implanted through natural or man-made openings in the maxillary sinus. In some embodiments, the spacer device is loaded with a therapeutic substance which then exits the device over a desired time period to treat maxillary sinus disease.

RELATED APPLICATIONS

This is a continuation in part of copending U.S. patent application Ser. No. 12/100,361 filed Apr. 9, 2008, which claims priority to U.S. Provisional Patent Application Ser. No. 60/922,730 Apr. 9, 2007 and is a continuation-in-part of U.S. patent application Ser. No. 11/544,009, filed Oct. 4, 2006, (issued as U.S. Pat. No. 7,419,497), which is a continuation in part of U.S. patent application Ser. No. 11/234,395, filed Sep. 23, 2005, (issued as U.S. Pat. No. 7,410,480), which is a continuation in part of U.S. patent application Ser. Nos. 10/829,917, filed Apr. 21, 2004, and 10/912,578 filed Aug. 4, 2004, (issued as U.S. Pat. No. 7,361,168). The full disclosure of each patent and patent application listed above is hereby expressly incorporated herein by reference.

TECHNICAL FIELD

The present application relates generally to medical devices and methods and more particularly to implantable devices for maintaining patency of maxillary sinus openings and/or delivering substances to treat maxillary sinus conditions.

BACKGROUND

In humans, the paranasal sinuses include several pairs of right and left sinus cavities, primarily the frontal, ethmoid, sphenoid and maxillary sinus cavities. Of these, the maxillary sinuses are the largest and the most common site for sinus infections.

The maxillary sinuses are located on either side of the nasal canal, below the eye socket and behind the cheekbone. Normally, each maxillary sinus has a natural ostium, which is an opening through which mucus drains from the sinus cavity into the nasal canal and through which air enters the sinus cavity. If the natural ostium of a maxillary sinus becomes obstructed due to microbial infection, chronic allergic inflammation or anatomical deformity (e.g., a deviated septum), the outflow of mucus and inflow of air may be impaired, thereby giving rise to a condition known as maxillary sinusitis. Less frequently, dental disease affecting the upper molar or bicuspid teeth, which are located just inferior to each maxillary sinus, may cause maxillary sinusitis.

In cases where maxillary sinusitis cannot be successfully treated with medical therapy (e.g., antibiotics, decongestants and steroid nasal sprays), surgery or catheter-based interventions are sometimes performed. The surgical approaches to treatment of maxillary sinusitis have included functional edoscopic sinus surgery (FESS), wherein an endoscope and various surgical instruments are inserted through the nostril and used to cut and/or remove bone and soft tissue in an effort to improve drainage and aeration of the maxillary sinus. In recent years, catheter-based approaches have been developed as alternatives to the cutting and removal of bone and soft tissue in the typical FESS procedure. In these catheter-based approaches, a dilator such as the balloon of a balloon catheter is maneuvered into the natural ostium of the maxillary sinus and used to dilate the natural ostium. Examples of such catheter-based procedures and related devices useable for treatment of maxillary sinusitis are described in U.S. Pat. Nos. 7,316,168; 7,500,971; 7,419,497; 7,462,175; and 7,410,408; and United States Patent Application Publication Nos. 2006/0004286; 2006/0063973; 2006/0210605; 2007/0129751; 2007/0135789; 2007/0167682; 2007/0208252; 2007/0208301; 2007/0293727; 2008/0097154; 2008/0097239; 2008/0097295; 2008/0097514; 2008/0097515; 2008/0097516; 2008/0103361; 2008/0103521; 2008/0119693; 2008/0125626; 2008/0154250; 2008/0195041; 2008/0228085; 2008/0234720; 2008/0187098; 2008/0275483; 2008/0281156; 2009/0030274; 2009/0093823 and 2009/0187089, the entire disclosures of which are expressly incorporated herein by reference.

As an alternative to, or in conjunction with, surgery or a catheter-based intervention of the type described above, various devices and methods have been proposed for delivering drugs or therapeutic agents into certain paranasal sinuses. For example, United States Patent Application Publication 2004/0116958A1 (Gopferich et al.) describes tubular spacers formed of biodegradable or non-biodegradable polymers and loaded with an active substance, such as a corticosteroid or anti-proliferative agent. After surgery has been performed to create a fenestration in a frontal sinus, the space is placed in such fenestration, and the active substance then passes out of the spacer. Also, Tarasov D I, et al., “Application of Drugs Based on Polymers in the Treatment of Acute and Chronic Maxillary Sinusitis,” Vestn Otorinolaringol. 1978; 6:45-47 has reported the delivery of drugs directly into a maxillary sinus cavity for treatment of sinusitis. Additionally, Deutschmann R, et al., “A Contribution to the Topical Treatment of [Maxillary] Sinusitis Preliminary Communication,” Stomat. 1976; DDR26:585-92 describes the instillation of a water soluble gelatin mixed with the drug (i.e., Chloramphenicol) into the maxillary sinus cavity for treatment of maxillary sinusitis. Since this gelatin/drug preparation was relatively short acting, the authors reported that in order to achieve a therapeutic effect it should be instilled every 2 to 3 days. Devices and methods for sustained delivery of drugs into paranasal sinus cavities are also described in U.S. Pat. Nos. 3,948,254 (Zafferoni); 5,512,055 (Domb, et al.); 7,361,168 (Makower, et al.); 7,410,480 (Muni et al.); and 7,419,497 (Muni, et al.); and United States Patent Application Publication Nos.: 2003/0185872A2 (Kochinke); 2005/0245906A1 (Makower, et al.); 2005/0043706 (Eaton, et al.); U.S. 2006/0106361A1 (Muni, et al.); 2007/0005094 (Eaton, et al.); 2008/0015540 (Muni et al.); 2008/0287908 (Muni et al.); 2008/0319424 (Muni et al.); 2009/0028923 (Muni, et al.); 2009/0017090 (Arensdorf, et al.); 2009/0047326 (Eaton, et al.); 2009/0156980 (Eaton, et al.) and 2009/0227945 (Eaton, et al.), as well as PCT International Patent Application Publication WO 92/15286 (Shikani).

There remains a need for the development of new devices and methods capable of improving drainage and/or aeration of a maxillary sinus and/or delivering therapeutic substance(s) into a maxillary sinus.

SUMMARY

In one aspect of the present invention, a method for treating a disorder of a maxillary sinus in a human or animal subject may include: forming an opening into a maxillary sinus; advancing a sinus spacer device at least partway through the opening; deploying at least one retention member of the spacer device to retain at least part of the spacer device within the maxillary sinus; introducing a substance into the spacer device to expand the device from a collapsed to an expanded configuration; and leaving the spacer device in the subject for a period of between 1 day and 60 days to allow the introduced substance to exit the spacer device and treat the disorder. In some embodiments of this method, the opening into the maxillary sinus may be an opening formed between the nasal cavity and a maxillary sinus, through a wall of the sinus. Such opening may be formed by any suitable means, including by inserting a penetrator through an inferior or middle nasal meatus and using the penetrator to penetrate through an adjacent wall of the maxillary sinus. In other embodiments of this method, the opening into a maxillary sinus may be an opening between the oral cavity and the maxillary sinus (e.g., an opening formed through the buccal or canine fossa). In some embodiments of the method, the opening may be formed at a downward angle to deter gravity-induced slippage of the spacer device after it has been placed through the opening.

In another aspect of the invention, a penetrator that is useable for forming an opening through a wall of a maxillary sinus may include a shaft that has a penetrating distal end and a curve of about 80 degrees to about 110 degrees formed in the shaft. In some embodiments, the penetrator may be equipped with sensors, reflectors or other apparatus so that it may be used in conjunction with an image guidance system, and the formation of the opening may be performed as an image guided procedure. In some embodiments, the penetrator may have indicator flag on or near the proximal end of the penetrator for indicating the direction of a curve in the penetrator shaft such that the operator may use the flag to determine or confirm the direction of the penetrator curve while the penetrator is inserted in the subject's body.

In some embodiments, the penetrator may have a lumen. After the penetrator has been used to penetrate through a wall of the maxillary sinus, a device or substance may be delivered through the penetrator lumen. For example, a guide member (e.g. a guidewire) may be advanced through the lumen of the penetrator, through the opening and into the maxillary sinus. Thereafter, the spacer device may be advanced over that guide member.

In another aspect of the invention, a tubular guide device may be used to facilitate placement of the spacer within the opening. Such tubular guide device may comprise a tubular shaft having a curve of approximately 80 degrees to about 110 degrees, and typically approximately 90 degrees to approximately 100 degrees, formed in a distal portion of the shaft. After the penetrator has been used to form the opening, the penetrator may be removed, and the tubular guide may then be advanced to a position where its distal end is within or aligned with the opening. The spacer device may then be advanced through the tubular guide, and the tubular guide may be removed, leaving the spacer device positioned within the opening or maxillary sinus.

In another aspect of the present invention, the spacer device may comprise an elongate member having a lumen into which a stylet is inserted. A stylet may be inserted into the lumen of the elongate shaft and the spacer, with the stylet positioned therein, may then be advanced through the opening. Thereafter, the stylet may be removed. The stylet may comprise an elongate shaft having a proximal end, a distal end and a hub (e.g., a Luer hub) on its proximal end. The shaft of the stylet may be continually tapered in diameter, or may comprise a series of regions of progressively smaller diameter, from proximal end to distal end.

In some embodiments, the spacer may comprise an elongate shaft and an expandable reservoir (e.g., a balloon). The expandable reservoir may be constructed such that a substance introduced into the reservoir will pass out of (or “exit”) the reservoir while it is implanted within the maxillary sinus. Examples of spacer devices of this type include the Relieva Stratus™ Microflow Spacer, available commercially from Acclarent, Inc., Menlo Park, Calif., as well as those described in U.S. Pat. Nos. 7,361,168; 7,410,480 and 7,419,497 and U.S. patent application Ser. Nos. 12/100,361 and 12/341,602, the entire disclosures of which are expressly incorporated herein by reference.

The reservoir of the spacer device may initially have a relatively small cross-sectional profile for delivery through the opening formed in the maxillary sinus wall. Thereafter, a fluid (e.g., saline) and/or an active substance (e.g., drug, biologic, or other therapeutic) may be introduced into the reservoir causing the reservoir to expand in situ. In at least some embodiments, the reservoir may be constructed so that it expands to a diameter of from about 3 mm to about 8 mm and a length of from about 1 mm to about 100 mm. The permeability of the reservoir may vary depending on the rate and time over which it is desired for the substance to exit the reservoir. For example, in some embodiments, the reservoir may be constructed such that the substance will continue to exit the reservoir for between about 14 days and about 21 days.

The spacer device may additionally comprise at least one position maintaining member that abuts, engages or attaches to an adjacent anatomical structure after being deployed to substantially maintain the reservoir in a location within the maxillary sinus. In some embodiments, the position maintaining member(s) may comprise a suture receiving member (e.g., a loop, slot, bar, etc.) for attaching the device to an adjacent anatomical structure by way of a suture or other connector (e.g., staple, clip, etc.). Additionally or alternatively, the position maintaining member(s) may comprise one or more projections (e.g., arms) that protrude from the device such that they will abut or engage (e.g., frictionally engage or exert pressure upon) an adjacent anatomical structure thereby substantially holding the device at the desired implantation location. Such projection(s) may be maintained in a collapsed position while at least part of the spacer device is inserted through the opening and, thereafter, such projection(s) may be caused to transition to extended position(s) whereby the projection(s) will mechanically contact at least one adjacent anatomical structure. In some embodiments, such projection(s) may comprise first and second laterally opposed projections (e.g., wire loops or wings) that, when in their extended positions, span a diameter of about 14 mm to about 20 mm.

In another aspect of the invention, a method for treating a disorder of a maxillary sinus in a human or animal subject may involve: dilating the maxillary sinus ostium; advancing a sinus spacer device (such as the spacer device summarized above) at least partway through the maxillary sinus ostium; deploying at least one retention member of the spacer device to retain at least part of the spacer device within the maxillary sinus; introducing a substance into the spacer device to expand the device from a collapsed to an expanded configuration; and leaving the spacer device in the subject for a period of between 1 day and 60 days to allow the introduced substance to exit the spacer device and treat the disorder. The dilation of the maxillary sinus ostium, which may include dilation of the ethmoid infundibulum, may be carried out by positioning an expandable dilator (e.g., a balloon) within the maxillary sinus ostium and, thereafter, expanding the dilator. Specific examples of dilation devices and methods that may be used for this dilation include the Relieva® Sinus Guide Catheters, Relieva® Sinus Balloon Catheters and Relieva Solo Pro™ Sinus Balloon Catheters, available commercially from Acclarent, Inc., Menlo Park, Calif. and devices described in the above-incorporated United States Patents and Patent Application Publications.

Additional aspects and details of various embodiments are set forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a side view of one embodiment of a substance delivery system comprising a spacer device in combination with a stylet.

FIG. 1B is a sectional view of the distal end of the spacer device of FIG. 1A during infusion of a substance into the expandable reservoir of the device.

FIG. 1C is a sectional view of the distal end of the spacer device of FIG. 1A after the expandable reservoir of the device has been filled with a substance.

FIG. 2 is a side view of the stylet of FIG. 1A.

FIG. 3 is a sectional side view of a guide catheter useable in conjunction with the system of FIG. 1A.

FIG. 4 is a side view of a maxillary insertion probe device useable in performing methods according to various embodiments.

FIGS. 5A through 5G show steps in one embodiment of a method in which a spacer device is implanted through an opening formed in a wall of a maxillary sinus between the sinus cavity and the nasal cavity.

FIG. 6 is a sectional view of a maxillary sinus ostium showing another embodiment of a method in which a spacer device is implanted through the ostium of a maxillary sinus.

FIG. 7 is a sectional view of a maxillary sinus ostium showing another embodiment of a method in which a spacer device is implanted through an opening formed in a wall of a maxillary sinus between the sinus cavity and the nasal cavity.

DETAILED DESCRIPTION

The following detailed description and the accompanying drawings to which it refers are intended to describe some, but not necessarily all, examples or embodiments of the invention. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The contents of this detailed description and the accompanying drawings do not limit the scope of the invention in any way.

Spacer/Stylet System:

Referring to FIG. 1A, in one embodiment, embodiment of a system 10 for treating a maxillary sinus may include an implantable spacer device 11 in combination with a stylet 40. (Only the hub 42 of the stylet 40 is visible in FIG. 1A, but further detail is provided in FIG. 2.) Some embodiments of the system 10 may further include a maxillary insertion guide 50 (FIG. 3) and/or a maxillary insertion probe 60 (FIG. 4).

In one embodiment, the spacer device 11 comprises an elongate flexible catheter shaft 12 comprising a proximal shaft portion 12 a and a distal shaft portion 12 b, which may be severed from one another at separation marker 15 or elsewhere along the shaft 12. The proximal shaft portion 12 a and distal shaft portion 12 b may be formed of the same or different materials and may have the same or different dimensions (e.g., diameter, wall thickness, etc.). For example, in some embodiments, the proximal shaft portion 12 a may be made of a suitable biocompatible material such as polyamide. In some embodiments, the distal shaft portion 12 b may be made of a more flexible biocompatible material such as nylon. A lumen 13 extends continuously through the shaft portions 12 a, 12 b, and a plug 23 is mounted in its distal end. The plug 23 may comprise any suitable closure member, such as a closed end on the tube, an end cap, a mass within the end of the lumen 13, or any other suitable flow blocking member. In the particular example shown in the drawings, the plug 23 comprises a biocompatible polymeric adhesive disposed within the distal end of lumen 13.

An expandable reservoir 14 is mounted in a collapsed configuration on the distal shaft portion 12 b near its distal end. Details of the reservoir 14 are seen in FIGS. 1B and 1C. As shown, in this embodiment, the reservoir 14 comprises a balloon that has a cylindrical side wall wherein openings 31 are formed. The reservoir 14 may also be formed of any suitable biocompatible material and, in some embodiments, may comprise a balloon formed of non-compliant or semi-compliant material such as Nylon 12. The size of the reservoir 14, the number of reservoirs (such as two or more), and the number and size of the openings 31 may vary on the basis of the intended implantation location and/or the potency, viscosity (or particle size) and/or other properties of the substance being delivered. For example, in an embodiment of the spacer device 11 intended to be passed through an ethmoidotomy channel and positioned within an ethmoid air cell to treat ethmoid sinusitis, the reservoir 14 may have a length of from about 0.5 cm to about 3.5 cm and typically approximately 2 cm, and a diameter when fully expanded of about 0.1 cm to about 0.5 cm and typically approximately 0.3 cm. In various embodiments, the reservoir 14 may include from about 50 to about 5000 openings, and each opening may have a diameter from about 5 microns to about 80 microns. In one embodiment, for example, the reservoir 14 includes about 2200 laser cut openings 31 approximately 20 microns in diameter formed in the sidewall of the reservoir 14. The openings 31 can be staggered one row to the next along the reservoir 14, and there also can be openings in the angled or tapered portions of the reservoir 14.

In various embodiments, the reservoir 14 may be used to deliver a desired therapeutic agent or drug at a desired rate over a desired time period. For example, in one embodiment, the reservoir 14 may be used to deliver approximately 0.10 ml of a 40 mg/ml of Triamcinolone Acetonide injectable suspension, USP (Kenalog®-40, Bristol-Myers Squibb, Somerville, N.J.), Approximately 100 μg of Triamcinolone will exit this embodiment of the reservoir 14 per day over a period of 14 days.

When used for the treatment of microbial infections, the reservoir 14 may be used to deliver a suitable antimicrobial agent (e.g., antibiotic or antifungal) alone or in combination with an antiinflammatory, such as a corticosteroid. For example, in patients suffering from maxillary sinusitis of fungal origin, the reservoir 14 may be used to deliver an antifungal agent, such as liposomal or non-liposomal Amphotericin B of 0.3 to 1.5 mg/kg, available from Pfizer as Amphocin® anti-fungal. Systemically administered Amphotericin typically has limited distribution from the bloodstream across the mucous membranes and vice versa. With this substance delivery spacer device 11, Amphotericin may be released locally into the mucous membrane where the offending fungal organisms are present, and therapeutic concentrations of the drug may remain in the mucus as it is distributed through the sinuses by ciliary action. However, substantial amounts of the Amphotericin will not be substantially absorbed through the sinus mucosa, thereby avoiding the potential for untoward systemic effects of the Amphotericin such as renal toxicity. Also, this reservoir 14 may be capable of delivering solutions as well as suspensions to the surrounding anatomy. This is especially useful for delivery of steroids since most steroids are available as suspensions.

Also, the reservoir 14 may act as a space occupying device (e.g., a stent) after expansion and may itself frictionally engage adjacent anatomical structure(s) to provide a degree of retention at the desired implantation location. This aspect of the reservoir 14 may be further facilitated by the provision of surface projections on the reservoir 14. In applications where it is intended only to perform a space occupying function, the reservoir 14 may be loaded with a biologically inert fluid (e.g., saline solution) rather than a solution or suspension that contains an active therapeutic agent.

The reservoir 14 also has the advantage of being relatively small in diameter when empty (e.g., collapsed or deflated) and thus can be introduced or removed easily. In embodiments where the reservoir 14 is formed of non-compliant or semi-compliant material, the reservoir 14 will not undergo substantial elastic deformation in the filling process and thus will not exert pressure on its contents in order to expel the desired substance through openings 31. Rather, the substance in the reservoir 14 will be carried out through the openings 31 by gravity or by being in contact with the mucus that is continually moved along by the ciliary action in the sinuses. This non-pressurized delivery allows for the slow release of the desired substance over several days.

In some other embodiments, the reservoir 14 may be formed of compliant or elastic material with small openings 31 such that the material of which the balloon 14 is formed will contract as substance passes out of the openings 31, thereby maintaining pressure within the balloon. In one embodiment, for example, the reservoir 14 may be 3.0 to 3.5 mm in diameter by 13 mm in length. The reservoir 14 may be made of Nylon 12. In this embodiment, approximately 768 laser cut openings 31 are formed in the side wall of the reservoir 14. The diameter of each laser cut opening 31 is 30 microns. The distal end of shaft 12 is plugged as shown using Dymax 204CTH adhesive. The distal portion of the shaft 12 is made of Nylon 12 of an outer diameter of about 0.028 inches and inner diameter of about 0.020 inches and length of about 17 mm. Elastomeric sleeve valve 26 is made of a 3 mm long C-flex medical grade TPE tubing. The tubing may have an inner diameter of about 0.022 inches and wall thickness of about 0.005 inches. Distal radiopaque marker 24 and proximal radiopaque marker 22 are made of a ring of Pt—Ir alloy of outer diameter about 0.034 inches and inner diameter about 0.030 inches. The proximal portion of the shaft 12 may be made of polyimide tubing of outer diameter about 0.0618 inches and inner diameter about 0.052 inches and length about 20 cm. In one embodiment, a hub 54 (see FIG. 3) is a female Luer hub made of clear polycarbonate made by Qosina (Edgewood, N.Y.) part number 41519. In one embodiment, each retention wing 18 is made of a bent loop of Nitinol wire having a diameter of about 0.0086 inches The retention wings are oriented at 80° to 90° from the longitudinal axis of the device. A heat treatment of 520° C. for 20 minutes of the nitinol wire loop produces an A_(f) of 20° C. Such a design of the substance delivery device 11 delivers approximately 100 μg per day of Kenalog®-40 over a period of 14 days.

In one embodiment, the exterior surface of reservoir 14 may be coated with a fracturable coating containing one or more therapeutic substances in a biodegradable matrix. When the reservoir 14 is filled, it expands. This expansion will fracture the fracturable coating such that pieces of the coating will enter the surrounding anatomy and will thereafter release the therapeutic substance(s) into the anatomy. The fracturable coating may be made, for example, from gelatin, sodium carboxymethyl cellulose or high molecular weight polyethylene glycol (PEG). Such a fracturable coating typically dissolves in an aqueous environment.

Referring again to FIGS. 1B and 1C, one embodiment includes an aperture 28 in the catheter shaft 12 to facilitate filling the reservoir 14. A valve 26 allows the substance (or component(s) of the substance) to flow from the lumen 13 of the catheter shaft 12 into the reservoir 14 (see FIG. 1C) but does not allow substantial backflow from the reservoir 14 into the lumen 13 (see FIG. 1B). The valve 26 may comprise any suitable type of one way valve. In the particular embodiment shown, the valve 28 comprises an elastomeric sleeve valve made of C-flex® thermoplastic elastomer (Consolidated Polymer Technologies, Inc., Clearwater, Fla.).

In some embodiments, radiopaque markers 22 and 24 are mounted on the distal catheter shaft portion 12 b to mark the proximal and distal ends of the reservoir 14. The radiopaque markers 22, 24 are preferably formed of material that is clearly more radiopaque than the adjacent materials and tissues. In this particular non-limiting example the markers 22, 24 are formed of Platinum-Iridium alloy.

Referring again to FIG. 1A, the spacer device 11 may incorporate position maintaining member(s) for holding the device at a desired location within a subject's body. In the non-limiting example shown, the position maintaining members include a suture loop 20 (e.g., an eyelet) as well as a plurality of projections 18 (e.g., retention wings). The suture loop 20 and projections 18 may be formed of supple, flexible, resilient, elastic or superelastic material such as nickel-titanium alloy (Nitinol) so that they may be collapsed. The projections 18 may be biased to a deployed (e.g., outwardly protruding) position as seen in FIG. 1A but may sometimes be compressed or bent to a non-deployed (e.g., collapsed) configuration in which they are substantially parallel and adjacent to the outer surface of the catheter shaft 12. In this manner, as described more fully below, these projections 18 may be constrained in their non-deployed position during insertion and positioning of the spacer device 11, and thereafter the constraint may be removed (e.g., as the distal portion of the device emerges out of the distal end of a guide catheter or other tubular delivery guide) allowing these projections 18 to spring to or otherwise assume their deployed positions where they will abut or engage (e.g., frictionally engage) adjacent anatomical structure(s).

In the particular example shown, the projections 18 are located proximal to reservoir 14 and are in the form of two (2) loops of wire (e.g., nickel-titanium wire) of 0.0086 inch diameter bent to form diametrically opposed retention wings. Projections 18 can also be located distal to the reservoir or both proximal and distal. When the projections 18 are nitinol, cold or warm fluid can be used to transition them to a “softer” state. The length of each projection 18 is determined based on the intended implantation site. For example, in applications where the device is inserted through an opening that is less than about 12 mm wide, the projections 18 may be sized such that they span a diameter of about 14 mm to about 20 mm when in their deployed positions, thus deterring slippage of the spacer device 11 out of the opening unless and until sufficient extraction force is applied to overcome the bias of the projections 18. The length and shape of the projections 18 may also be designed to cause minimal trauma to the anatomy while ensuring the maximum retention of the spacer device 11 at its intended implantation location. In the example shown, the wire loops that form the projections 18 and suture loop 20 may be affixed to the outer surface of shaft 12 by winding the wire around the shaft and securing the wire to the shaft using a suitable adhesive such as cyanoacrylate, epoxy or UV curable adhesive and/or by mounting a polymeric sleeve or heat shrinkable member about the portions of wire that are wound around the shaft 12.

The position maintaining member(s), in one embodiment, comprise small retention wing(s) made of nitinol wire that spring outward inside of the sinus cavity, but also have a relatively light spring force so that the device can be out and removed when desired. Beneficially, the spacer device 11 can be removed in a physician's office rather than a surgical setting.

Optionally, a flexible distal member 17 (FIG. 1A) may be continuation of, or may extend from, the distal end of the shaft 12 b. This optional distal member 17 may have a length of from about 1 cm to about 5 cm and may facilitate passage of the spacer device 11 through the intended opening. In embodiments where the distal portion 17 is of sufficient length, it may become coiled or convoluted within the sinus cavity when the spacer device 11 is implanted and, thus, may function as an additional means for deterring slippage or migration of the spacer device 11 while it is implanted.

FIG. 2 shows details of the stylet 40. The stylet 40 comprises an elongate shaft 44 and a hub member 42 on the proximal end of the shaft 44. The shaft 44 is sized to be advanced into lumen 13 of the spacer device 11 to facilitate insertion of the spacer device 11, as described more fully below. The stylet shaft 44 may be formed of any suitable material and may be of any suitable construction. In this particular example, the shaft 44 may be formed of nickel-titanium alloy wire that has been machined to a series of regions 44 a, 44 b, 44 c, 44 d, 44 e that are progressively smaller in diameter, thereby giving the distal portion of the shaft 44 greater flexibility than the proximal portion. In the particular example shown, the shaft 44 steps down from a diameter of about 0.033 inch in the proximal shaft region 44 a to a diameter of about 0.010 inch at the distal end of the distal shaft region 44 e. The proximal hub member 42 is configured to abut or seat within he proximal Luer connector 16 of the spacer device 11 when the stylet 40 is fully inserted into the spacer device 11. The length of the stylet shaft 44 may be such that, when the hub 42 is firmly seated within the proximal Luer connector 16 of the spacer device 11, the distal end of the stylet shaft 44 will contact or be positioned close to the proximal surface of plug member 23. In this manner the stylet shaft 44 will occupy all or substantially all of the elongate spacer 12 during its insertion.

Maxillary Insertion Guide:

FIG. 3 shows one embodiment of a maxillary insertion guide 50 for facilitating insertion of the spacer/stylet system 10 through an opening formed in the medial wall of a maxillary sinus. The guide 50 comprises an elongate shaft 52 having a proximal hub 54 at its proximal end PE, a straight proximal portion PP and a curved distal portion DP. Any suitable shaft construction may be used. In this particular example, the proximal portion PP of the shaft 52 comprises an outer tube 56, an inner tube 58 and an inner liner 59 that lines the inner wall of the inner tube 58. The outer tube 56 in this example is formed of stainless steel hypotube having an outer diameter of about 0.134 inch and a length of about 85 mm. The inner tube 58 in this example comprises nylon tubing having an inner diameter of about 0.087 inch. The liner 59 comprises thin polytetrofluoroethylene (PTFE) tube. The distal portion DP of the shaft 52 comprises a segment of the inner tube 58 and liner 59 that protrudes out of and beyond the distal end of the outer tube 56, as shown. Optionally, the distal-most 3-4 mm of this distal portion DP may be formed of a material (e.g., an elastomer or hydrogel) that is softer than the material of the inner tube 58 to deter trauma or abrasion of tissue during insertion of the device. In this non-limiting example, the distal portion DP of the shaft 52 has a length of about 22 mm, an outer diameter of about 0.109 inch and an inner diameter of about 0.087 inch. A curve of about 90 degrees to about 100 degrees, with a radius of curvature of about 0.3 to about 0.375, is formed in the distal portion DP of the shaft 52.

The inner tube 58 extends through the lumen of the outer tube 56 and a distal portion of the inner liner 59 protrudes out of the distal end of the outer tube 56. This distal portion of the inner liner 59 protrudes out of the distal end of the inner tube 58 is bent to form the desired curve. In this non-limiting example, the protruding inner liner 59 of the inner tube 58 is rigid enough to maintain the desired curved shape but flexible enough to prevent or reduce unnecessary trauma to the anatomy during use. Also, the inner liner 59 may be rigid enough to enable a user to volitionally displace adjacent paranasal structures as it is being inserted and maneuvered into position.

One or more radiopaque or visual markers may be provided on this guide device 50 to facilitate its positioning during use.

Maxillary Insertion Probe:

FIG. 4 shows an example of a maxillary insertion probe 60 that may be used to form an opening through a wall of a maxillary sinus. This probe 60 comprises an elongate rigid shaft 62 having a handpiece 64 on its proximal end and a sharp distal tip 68 at its distal end. A curve 66 of approximately 90 degrees to about 110 degrees is formed in the elongate shaft 62 near its distal tip.

Examples of Methods for Treatment of Maxillary Sinusitis: Example 1 Placement of Spacer Through Antro-Nasal Opening

FIGS. 5A through 5G show one non-limiting example of a method treating maxillary sinusitis by forming an opening 70 through a wall W of a maxillary sinus MS and implanting the spacer device 11 such that its reservoir 14 is within the maxillary sinus MS.

In many subjects, approximately the middle third of the medial wall of the maxillary sinus MS also serves as the lateral wall of the inferior meatus IM. In this example, the maxillary insertion probe 60 is inserted through a nostril and is advanced through the inferior meatus IM to a position where the sharp distal tip 68 of the maxillary insertion probe 60 is positioned in contact with the lateral aspect of the inferior meatus IM forming the maxillary sinus wall W. Optionally, if necessary, the inferior turbinate IT may be medialized. However, in most subjects the devices used will be sized to perform this procedure without requiring breaking or medialization of the inferior turbinate IT.

The sharp distal tip 68 of the maxillary insertion probe 60 is then pushed through the maxillary sinus wall W as shown in FIG. 5A, thereby creating an opening 70 (FIG. 5B) through the wall W. The maxillary insertion probe 60 is then removed, as shown in FIG. 5B. Thereafter, as seen in FIG. 5C, the maxillary delivery guide 50 is inserted into the inferior meatus IM and advanced to a position where its distal end DE is within or aligned with the opening 70 in the wall W of the maxillary sinus MS. Thereafter, as shown in FIG. 5D, the spacer device 11 with the stylet shaft 44 inserted therein is advanced through the guide 50 such that the reservoir 14 and retention members 18 enter the sinus cavity. As the retention members 18 emerge out of the lumen of the guide 60 they will spring outwardly to their deployed positions. When so deployed, the retention members 18 will span a width that is greater than the diameter of the opening 70, thereby deterring slippage of the spacer device 11 out of the maxillary sinus MS. Thereafter, the stylet shaft 44 is retracted and the stylet 40 is removed.

As seen in FIG. 5F, a syringe or other infusion device is then attached to the Luer connector of the spacer device 11 and is used to infuse a desired substance into the reservoir 14, thereby causing the reservoir to expand. In some cases, a biologically inert fluid (e.g., saline solution) may be used. In other cases, a fluid containing an active substance may be infused so that the active substance will subsequently pass out of the reservoir 14 into the maxillary sinus MS over a desired time period. For example, if used to deliver Triamcinolone Acetonide Injectable Suspension, USP (Kenalog®-40, Bristol-Myers Squibb, Somerville, N.J.), the reservoir 14 may have an overall length of about 16 mm and a working length (i.e., the length of the cylindrical side wall 14 c) of about 13 mm and may be expandable to a fully expanded diameter of 3.0 to 3.5 mm. Approximately 768 laser cut openings 31 may be formed in the side wall of the reservoir 14 with the diameter of each such opening 31 being about 40 microns. This particular reservoir design, when loaded with 0.31 to 0.35 ml of the 40 mg/ml Triamcinolone Acetonide injectable suspension, will deliver a dose of approximately 100 μg Triamcinolone Acetonide per day for a period of about 28 days into the maxillary sinus MS.

As seen in FIG. 5G, after the desired substance has been loaded into the reservoir, the proximal shaft portion 12 a is cut away or otherwise detached from the distal shaft portion 12 b. Optionally, the remaining distal shaft portion 12 b may be affixed to an adjacent anatomical structure within the nose to further secure the positioning of the implant. In the non-limiting example shown in FIG. 5G, this is accomplished by suturing the suture loop 20 to the intranasal septum S.

The implanted portion of the device 12 may remain in place for a desired time period and then may be removed. For example, in applications where the reservoir 14 is loaded with a steroid and/or antimicrobial agent for treatment of chronic maxillary sinusitis, it will typically be desirable for the implanted portion of the device 12 to remain in place with the active substance(s) exiting the reservoir for approximately 14-28 days. In some subjects, the implanted portion of the device 12 may be allowed to remain in place to perform a spacer function (e.g., maintaining patency of the opening 70) even after any active substance has passed out of and been depleted from the reservoir 14.

Example 2 Placement of Spacer Through Maxillary Sinus Ostium with or without Enlargement of the Ostium

In another embodiment of the present invention, as shown in FIG. 6, the spacer device 11 may be implanted through the maxillary ostium MO of a maxillary sinus MS, with or without dilation or surgical modification of the natural ostium MO.

Each maxillary sinus has a natural maxillary sinus ostium MO through which secretions drain from the maxillary sinus cavity into the nose. The natural ostium is formed by an opening in bone (which is normally intact and unfractured) covered by soft tissue (mucosal tissue). In some individuals one or more accessory ostia may also be present. Due to the anatomical position of the maxillary ostium, gravity cannot normally drain mucus from the sinus cavity when the subject's head is erect. Thus, ciliary transport of mucus is necessary to clear mucus from the sinus cavity. The maxillary sinus cavity is normally lined with a ciliated soft tissue known as mucoperiosteum. Typically, the cilia transport mucus in a stellate or star-like pattern that originals from the floor of the sinus cavity, radiates over the anterior, medial, posterior, lateral and upper walls of the sinus cavity, and converges at the natural ostium (or ostia). The mucus then drains through the natural ostium and into the nose. Also, air normally enters the maxillary sinus cavity through the ostium. When the natural ostium becomes obstructed or stenotic, the normal drainage of mucus and aeration of the maxillary sinus cavity is impaired, and chronic sinusitis can result.

Sinus surgery is sometimes performed, in which bone and soft tissue are cut away to enlarge the natural ostium. Also, the natural ostium of a maxillary sinus may be enlarged by a technique known as Balloon Sinuplasty™ (Acclarent, Inc., Menlo Park, Calif.) wherein a pre-shaped guide catheter is inserted into the nose and a balloon dilation catheter is then advanced through the guide catheter. A balloon of the balloon catheter is positioned within the maxillary sinus ostium and inflated, thereby dilation the natural ostium. This dilation typically causes fracture or other movement of bone (i.e., intact, unfractured bone) that, together with overlying soft tissue, defines the ostium. Maxillary sinus guide catheters that are useable for guiding a balloon dilation catheter into the maxillary ostium are available commercially as Relieva® Sinus Guide Catheters (Acclarent, Inc., Menlo Park, Calif.). Details regarding the construction and configuration of these maxillary guide catheters and details regarding balloon dilation of the maxillary sinus ostium are found in above-incorporated United States Patents and United States Patent Application Publications. As described in this example, these maxillary sinus guide catheters may also be used to guide placement of a spacer device 11 of the present invention through a maxillary sinus ostium.

In this embodiment of the present invention, a maxillary sinus guide such as the type commercially available and described above is advanced into the middle meatus MM and positioned within or in alignment with the maxillary sinus ostium. Optionally, a balloon dilation catheter (e.g., Relieva Solo Prom™ Sinus Balloon Catheter, Acclarent, Inc., Menlo Park, Calif.) may be advanced through the maxillary sinus guide, positioned within the ostium, used to dilate the ostium, and then removed, leaving the maxillary sinus guide in place. Alternatively, in some cases, surgery may have been performed to surgically enlarge the maxillary ostium prior to placement of the maxillary sinus guide catheter.

The spacer device 11, with the stylet shaft 44 inserted therein, is advanced through the maxillary sinus guide catheter so the reservoir 14 and retention members 18 enter the maxillary sinus MS. As the retention members 18 emerge out of the guide catheter they will spring outwardly to their deployed positions. When so deployed, the retention members 18 will span a width that is greater than the diameter of the natural or enlarged maxillary ostium, thereby deterring slippage of the spacer device 11 out of the maxillary sinus MS. Thereafter, the stylet shaft 44 is retracted and the stylet 40 is removed. A syringe or other infusion device is then attached to the Luer connector of the spacer device 11 and is used to infuse a desired substance into the reservoir 14, thereby causing the reservoir to expand, as seen in FIG. 6. In some cases, a biologically inert fluid (e.g., saline solution) may be used. In other cases, a fluid containing an active substance as described above may be infused so that the active substance will subsequently exit the reservoir 14 into the maxillary sinus MS over a desired time period.

After the desired substance has been loaded into the reservoir 14, the proximal shaft portion 12 a of the spacer device 11 is cut away or otherwise detached from the distal shaft portion 12 b. Optionally, the remaining distal shaft portion 12 b may be affixed to an adjacent anatomical structure within the nose to further secure the positioning of the implant. In the non-limiting example shown in FIG. 6, this is accomplished by suturing the suture loop 20 to the intranasal septum S.

The implanted portion of the device 12 may remain in place for a desired time period and then may be removed. As explained above, in applications where the reservoir 14 is loaded with a steroid and/or antimicrobial agent for treatment of chronic maxillary sinusitis, it will typically be desirable for the implanted portion of the device 12 to remain in place with the active substance(s) passing out of the reservoir for approximately 14-28 days. In some subjects, the implanted portion of the device 12 may be allowed to remain in place to perform a spacer function (e.g., maintaining patency of the opening 70) even after any active substance has passed out of and been depleted from the reservoir 14.

Example 3 Placement of Spacer Through Opening in Canine or Buccal Fossa

Techniques have been well established for creating openings (e.g., puncture tracts) between the oral cavity and the maxillary sinus. Typically, such techniques involve the creation of an opening through the canine or buccal fossa and into the maxillary sinus cavity. In the example shown in FIG. 7, an opening is made through the canine fossa CF above the teeth T and the spacer device 11 with the stylet shaft 44 inserted therein is advanced through that opening such that the reservoir 14 and retention members 18 enter the sinus cavity. This may be facilitated by insertion of a tubular guide, such as a straight rigid tube, into the canine fossa opening and then advancing the spacer device 11/stylet shaft 44 through that tubular guide. As the retention members 18 emerge out of the lumen of the guide 60 they will spring outwardly to their deployed positions. When so deployed, the retention members 18 will span a width that is greater than the diameter of the canine fossa opening, thereby deterring slippage of the spacer device 11 out of the maxillary sinus MS. Thereafter, the stylet shaft 44 is retracted and the stylet 40 is removed.

A syringe or other infusion device is then attached to the Luer connector of the spacer device 11 and is used to infuse a desired substance into the reservoir 14, thereby causing the reservoir to expand. In some cases, a biologically inert fluid (e.g., saline solution) may be used. In other cases, a fluid containing an active substance may be infused so that the active substance will subsequently pass out of the reservoir 14 into the maxillary sinus MS over a desired time period. For example, if used to deliver Triamcinolone Acetonide Injectable Suspension, USP (Kenalog®-40, Bristol-Myers Squibb, Somerville, N.J.), the reservoir 14 may have an overall length of about 16 mm and a working length (i.e., the length of the cylindrical side wall 14 c) of about 13 mm and may be expandable to a fully expanded diameter of 3.0 to 3.5 mm. Approximately 768 laser cut openings 31 may be formed in the side wall of the reservoir 14 with the diameter of each such opening 31 being 40 microns. This particular reservoir design, when loaded with 0.31 to 0.35 ml of the 40 mg/ml Triamcinolone Acetonide injectable suspension, will deliver a dose of approximately 100 μg Triamcinolone Acetonide per day for a period of 28 days into the maxillary sinus MS.

As seen in FIG. 7, after the desired substance has been loaded into the reservoir, the proximal shaft portion 12 a is cut away or otherwise detached from the distal shaft portion 12 b. Optionally, the remaining distal shaft portion 12 b may be affixed to an adjacent anatomical structure within the oral cavity to further secure the positioning of the implant. In the non-limiting example shown in FIG. 7, this is accomplished by suturing the suture loop 20 to the buccal mucosa above the teeth T.

The implanted portion of the device 12 may remain in place for a desired time period and then may be removed. For example, in applications where the reservoir 14 is loaded with a steroid and/or antimicrobial agent for treatment of chronic maxillary sinusitis, it will typically be desirable for the implanted portion of the device 12 to remain in place with the active substance(s) exiting the reservoir for approximately 14-28 days. In some subjects, the implanted portion of the device 12 may be allowed to remain in place to perform a spacer function (e.g., maintaining patency of the opening 70) even after any active substance has passed out of and been depleted from the reservoir 14.

The term “substance,” as used herein, is to be broadly construed to include any feasible drugs, prodrugs, proteins, gene therapy preparations, cells, diagnostic agents, contrast or imaging agents, biologicals, etc. Such substances may be in bound or free form, liquid or solid, colloid or other suspension, solution or may be in the form of a gas or other fluid or non-fluid. For example, in some applications where it is desired to treat or prevent a microbial infection, the substance delivered may comprise a pharmaceutically acceptable salt or dosage form of an antimicrobial agent (e.g., antibiotic, antiviral, antiparasitic, antifungal, etc.), a corticosteroid or other anti-inflammatory (e.g., an NSAID), a decongestant (e.g., vasoconstrictor), a mucus thinning agent (e.g., an expectorant or mucolytic), an agent that prevents of modifies an allergic response (e.g., an antihistamine, cytokine inhibitor, leucotriene inhibitor, IgE inhibitor, immunomodulator), an anesthetic agent with or without a vasoconstriction agents (e.g. Xylocalne with or without Epinephrine), an analgesic agent, an allergen or another substance that causes secretion of mucus by tissues, hemostatic agents to stop bleeding, anti-proliferative agents, cytotoxic agents e.g. alcohol, biological agents such as protein molecules, stem cells, genes or gene therapy preparations, viral vectors carrying proteins or nucleic acids such as DNA or mRNA coding for important therapeutic functions or substances, cauterizing agents e.g. silver nitrate, etc.

Some non-limiting examples of antimicrobial agents that may be used in this invention include acyclovir, amantadine, rimantadine, oseltamivir, zanamivir, aminoglycosides (e.g., amikacin, gentamicin and tobramycin), amoxicillin, amoxicillin/clavulanate, amphotericin B, ampicillin, ampicillin/sulbactam, atovaquone, azithromycin, cefazolin, cefepime, cefotaxime, cefotetan, cefpodoxime, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, cephalexin, chloramphenicol, clotrimazole, ciprofloxacin, clarithromycin, clindamycin, dapsone, dicloxacillin, doxycycline, erythromycin, fluconazole, foscarnet, ganciclovir, atifloxacin, imipenem/cilastatin, isoniazid, itraconazole, ketoconazole, metronidazole, nafcillin, nafcillin, nystatin, penicillins including penicillin G, pentamidine, piperacillin/tazobactam, rifampin, quinupristin-dalfopristin, ticarcillin/clavulanate, trimethoprim/sulfamethoxazole, valacyclovir, vancomycin, mafenide, silver sulfadiazine, mupirocin, nystatin, triamcinolone/nystatin, clotrimazole/betamethasone, clotrimazole, ketoconazole, butoconazole, miconazole, tioconazole, detergent-like chemicals that disrupt or disable microbes (e.g., nonoxynol-9, octoxynol-9, benzalkonium chloride, menfegol, and N-docasanol); chemicals that block microbial attachment to target cells and/or inhibits entry of infectious pathogens (e.g., sulphated and sulponated polymers such as PC-515 (carrageenan), Pro-2000, and Dextrin 2 Sulphate); antiretroviral agents (e.g., PMPA gel) that prevent retroviruses from replicating in the cells; genetically engineered or naturally occurring antibodies that combat pathogens such as anti-viral antibodies genetically engineered from plants known as “plantibodies;” agents which change the condition of the tissue to make it hostile to the pathogen (such as substances which alter mucosal pH (e.g., Buffer Gel and Acidform); non-pathogenic or “friendly” microbes that cause the production of hydrogen peroxide or other substances that kill or inhibit the growth of pathogenic microbes (e.g., lactobacillus); antimicrobial proteins or peptides such as those described in U.S. Pat. No. 6,716,813 (Lin et al.) which is expressly incorporated herein by reference or antimicrobial metals (e.g., colloidal silver).

Additionally or alternatively, in some applications where it is desired to treat or prevent inflammation the substances delivered in this invention may include various steroids or other anti-inflammatory agents (e.g., nonsteroidal anti-inflammatory agents or NSAIDs), analgesic agents or antipyretic agents. For example, corticosteroids that have previously administered by intranasal administration may be used, such as beclomethasone (Vancenase® or Beconase®), flunisolide (Nasalide®), fluticasone proprionate (Flonase®), triamcinolone acetonide (Nasacort®), budesonide (Rhinocort Aqua®), loterednol etabonate (Locort) and mometasone (Nasonex®). Other salt forms of the aforementioned corticosteroids may also be used. Also, other non-limiting examples of steroids that may be useable in the present invention include but are not limited to aclometasone, desonide, hydrocortisone, betamethasone, clocortolone, desoximetasone, fluocinolone, flurandrenolide, mometasone, prednicarbate; amcinonide, desoximetasone, diflorasone, fluocinolone, fluocinonide, halcinonide, clobetasol, augmented betamethasone, diflorasone, halobetasol, prednisone, dexamethasone and methylprednisolone. Other anti-inflammatory, analgesic or antipyretic agents that may be used include the nonselective COX inhibitors (e.g., salicylic acid derivatives, aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, sulfasalazine and olsalazine; para-aminophenol derivatives such as acetaminophen; indole and indene acetic acids such as indomethacin and sulindac; heteroaryl acetic acids such as tolmetin, dicofenac and ketorolac; arylpropionic acids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen and oxaprozin; anthranilic acids (fenamates) such as mefenamic acid and meloxicam; enolic acids such as the oxicams (piroxicam, meloxicam) and alkanones such as nabumetone) and Selective COX-2 Inhibitors (e.g., diaryl-substituted furanones such as rofecoxib; diaryl-substituted pyrazoles such as celecoxib; indole acetic acids such as etodolac and sulfonanilides such as nimesulide).

Additionally or alternatively, in some applications, such as those where it is desired to treat or prevent an allergic or immune response and/or cellular proliferation, the substances delivered in this invention may include a) various cytokine inhibitors such as humanized anti-cytokine antibodies, anti-cytokine receptor antibodies, recombinant (new cell resulting from genetic recombination) antagonists, or soluble receptors; b) various leucotriene modifiers such as zafirlukast, montelukast and zileuton; c) immunoglobulin E (IgE) inhibitors such as Omalizumab (an anti-IgE monoclonal antibody formerly called rhu Mab-E25) and secretory leukocyte protease inhibitor).

Additionally or alternatively, in some applications, such as those where it is desired to shrink mucosal tissue, cause decongestion or effect hemostasis, the substances delivered in this invention may include various vasoconstrictors for decongestant and or hemostatic purposes including but not limited to pseudoephedrine, xylometazoline, oxymetazoline, phenylephrine, epinephrine, etc.

Additionally or alternatively, in some applications, such as those where it is desired to facilitate the flow of mucus, the substances delivered in this invention may include various mucolytics or other agents that modify the viscosity or consistency of mucus or mucoid secretions, including but not limited to acetylcysteine (Mucomyst™, Mucosil™) and guaifenesin.

Additionally or alternatively, in some applications such as those where it is desired to prevent or deter histamine release, the substances delivered in this invention may include various mast cell stabilizers or drugs which prevent the release of histamine such as cromolyn (e.g., Nasal Chrom®) and nedocromil.

Additionally or alternatively, in some applications such as those where it is desired to prevent or inhibit the effect of histamine, the substances delivered in this invention may include various antihistamines such as azelastine (e.g., Astylin®), diphenhydramine, loratidine, etc.

Additionally or alternatively, in some embodiments such as those where it is desired to dissolve, degrade, cut, break or remodel bone or cartilage, the substances delivered in this invention may include substances that weaken or modify bone and/or cartilage to facilitate other procedures of this invention wherein bone or cartilage is remodeled, reshaped, broken or removed. One example of such an agent would be a calcium chelator such as EDTA that could be injected or delivered in a substance delivery implant next to a region of bone that is to be remodeled or modified. Another example would be a preparation consisting of or containing bone degrading cells such as osteoclasts. Other examples would include various enzymes of material that may soften or break down components of bone or cartilage such as collagenase (CGN), trypsin, trypsin/EDTA, hyaluronidase, and tosyllysylchloromethane (TLCM).

Additionally or alternatively, in some applications, the substances delivered in this invention may include other classes of substances that are used to treat rhinitis, nasal polyps, nasal inflammation, and other disorders of the ear, nose and throat including but not limited to anti-cholinergic agents that tend to dry up nasal secretions such as ipratropium (Atrovent Nasal®), as well as other agents not listed here.

Additionally or alternatively, in some applications such as those where it is desired to draw fluid from polyps or edematous tissue, the substances delivered in this invention may include locally or topically acting diuretics such as furosemide and/or hyperosmolar agents such as sodium chloride gel or other salt preparations that draw water from tissue or substances that directly or indirectly change the osmolar content of the mucus to cause more water to exit the tissue to shrink the polyps directly at their site.

Additionally or alternatively, in some applications such as those wherein it is desired to treat a tumor or cancerous lesion, the substances delivered in this invention may include antitumor agents (e.g., cancer chemotherapeutic agents, biological response modifiers, vascularization inhibitors, hormone receptor blockers, cryotherapeutic agents or other agents that destroy or inhibit neoplasia or tumorigenesis) such as; alkylating agents or other agents which directly kill cancer cells by attacking their DNA (e.g., cyclophosphamide, isophosphamide), nitrosoureas or other agents which kill cancer cells by inhibiting changes necessary for cellular DNA repair (e.g., carmustine (BCNU) and lomustine (CCNU)), antimetabolites and other agents that block cancer cell growth by interfering with certain cell functions, usually DNA synthesis (e.g., 6 mercaptopurine and 5-fluorouracil (5FU), antitumor antibiotics and other compounds that act by binding or intercalating DNA and preventing RNA synthesis (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin, mitomycin-C and bleomycin) plant (vinca) alkaloids and other anti-tumor agents derived from plants (e.g., vincristine and vinblastine), steroid hormones, hormone inhibitors, hormone receptor antagonists and other agents which affect the growth of hormone-responsive cancers (e.g., tamoxifen, herceptin, aromatase ingibitors such as aminoglutethamide and formestane, trriazole inhibitors such as letrozole and anastrazole, steroidal inhibitors such as exemestane), anti-angiogenic proteins, small molecules, gene therapies and/or other agents that inhibit angiogenesis or vascularization of tumors (e.g., meth-1, meth-2, thalidomide), bevacizumab (Avastin), squalamine, endostatin, angiostatin, Angiozyme, AE-941 (Neovastat), CC-5013 (Revimid), medi-522 (Vitaxin), 2-methoxyestradiol (2ME2, Panzem), carboxyamidotriazole (CAI), combretastatin A4 prodrug (CA4P), SU6668, SU11248, BMS-275291, COL-3, EMD 121974, IMC-1C11, IM862, TNP-470, celecoxib (Celebrex), rofecoxib (Vioxx), interferon alpha, interleukin-12 (IL-12) or any of the compounds identified in Science Vol. 289, Pages 1197-1201 (Aug. 17, 2000) which is expressly incorporated herein by reference, biological response modifiers (e.g., interferon, bacillus calmette-guerin (BCG), monoclonal antibodies, interluken 2, granulocyte colony stimulating factor (GCSF), etc.), PGDF receptor antagonists, herceptin, asparaginase, busulphan, carboplatin, cisplatin, carmustine, cchlorambucil, cytarabine, dacarbazine, etoposide, flucarbazine, fluorouracil, gemcitabine, hydroxyurea, ifosphamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, thioguanine, thiotepa, tomudex, topotecan, treosulfan, vinblastine, vincristine, mitoazitrone, oxaliplatin, procarbazine, streptocin, taxol, taxotere, analogs/congeners and derivatives of such compounds as well as other antitumor agents not listed here.

Additionally or alternatively, in some applications such as those where it is desired to grow new cells or to modify existing cells, the substances delivered in this invention may include cells (mucosal cells, fibroblasts, stem cells or genetically engineered cells) as well as genes and gene delivery vehicles like plasmids, adenoviral vectors or naked DNA, mRNA, etc. injected with genes that code for anti-inflammatory substances, etc., and, as mentioned above, osteoclasts that modify or soften bone when so desired.

The devices and methods disclosed herein may be used to deliver combinations of two or more substances. In one particular embodiment, the devices and methods disclosed herein may be used to deliver a combination of an anti-inflammatory agent (e.g. a steroid or an NSAID) and a mucolytic agent.

The devices and methods disclosed herein may be used to deliver gels or viscous liquids comprising one or more substances. Such gels or viscous liquids may coat and adhere to a mucous membrane and thus provide sustained delivery of one or more substances to the mucous membrane. In one embodiment, a plasticized hydrocarbon gel comprising gelatin, pectin and sodium carboxymethylcellulose and a suitable substance may be delivered to a mucous membrane such as the mucous membrane of a paranasal sinus. Such gels can be used for sustained delivery of the suitable substance to the mucous membrane.

The reservoir 14 of the devices described herein may optionally comprise multiple compartments such that each compartment stores a particular substance formulation. The multiple compartments prevent mixing of multiple substance formulations before substance formulations are delivered to the anatomy.

One or more of the substance reservoirs comprising holes or pores may be filled with a suitable substance at a sufficiently high pressure to cause a portion of the substance to squirt out of the holes or pores. This process may be used to deliver an initial bolus of the substance to the surrounding anatomy.

One or more of the substance reservoirs disclosed herein may be filled with a suitable substance after the substance reservoir is introduced in an anatomical region. Alternatively, one or more of the substance reservoirs disclosed herein may be filled with a suitable substance before the substance reservoir is introduced in an anatomical region. Alternatively, one or more of the substance reservoirs disclosed herein may be pre-filled with a solid, lyophilized or concentrated substance. The solid, lyophilized or concentrated substance is converted to an active form by introducing a solvent into the substance reservoir. This may be done just before or after the substance reservoir is introduced in an anatomical region. Alternatively, one or more of the substance reservoirs disclosed herein may be pre-filled with an inactive form of a substance. The inactive form of the substance is converted to an active form by introducing an activating agent into the substance reservoir. This may be done just before or after the substance reservoir is introduced in an anatomical region.

As described above, the implantable portion of a substance delivering spacer device 11 may include a through lumen that may function as a vent and/or drain when such implantable portion device is implanted in the body.

The distal-most regions of one or more substance delivery devices disclosed herein may comprise an atraumatic tip. The atraumatic tip is used to prevent or reduce damage to the anatomy by the distal-most regions of the one or more substance delivery devices.

The outer surface of one of more substance delivery devices disclosed herein may comprise a coating that reduces or eliminates the risk of encrusting of the outer surface by a biological material. In one embodiment, the coating comprises a material that absorbs water to form a gel. Examples of such materials include, but are not limited to hyaluronic acid, etc.

One or more of the substance delivery devices disclosed herein may be refilled after a significant volume of substance filled in a substance reservoir has been delivered. For example, in one embodiment a substance delivery device may include a proximal refilling port, which may be accessed using a needle and syringe. Such a port may self-seal after refilling via the needle. One embodiment may include a grasping member, which a physician may use to grasp the device using forceps or another instrument to hold the device during refilling.

One or more of the substance delivery devices disclosed herein may comprise one or more markers to enable a user to locate and/or navigate the substance delivery devices through the anatomy. For example, the substance delivery devices may comprise visual markers to enable the user to determine the depth of insertion of the substance delivery devices into the anatomy. In another example, the substance delivery devices may comprise imaging markers to enable the user to locate and/or navigate the substance delivery devices using imaging modalities such as X-rays, MRI, etc.

Although the examples above describe Triamcinolone Acetonide injectable suspension (Kenalog® 40, Brystol-Myers Squibb Company, Princeton, N.J.) as the therapeutic agent that is loaded into and passes out of the reservoir, various other therapeutic agents may be used in addition to, or as an alternative to, this Triamcinolone Acetonide injectable suspension. In some cases where it is desired to use the implanted spacer device 11 to deliver a steroid, the steroid may be prepared as a solution rather than a suspension. In such cases, the steroid will be dissolved in a suitable, biologically compatible solvent. For example, Cyclodextrins have been described as suitable solvents for dissolution of at least some steroids. Khomutov, S. M., Dovbnya, D. V. and Donova, M. V., Dissolution of a Mixture of Steroids in Cyclodextrin Solutions: a Model Description; Pharmaceutical Chemistry Journal; Vol. 35, No. 11, pp. 627-629 (November, 2001).

In some instances, the devices of the present invention may be used to deliver steroids or other substances in formulations that are commercially available as, or otherwise suitable for, intra-nasal delivery to the nasal mucosa as nasal drops or sprays (i.e., nasal solutions). In at least some cases, such nasal solutions are prepared so that they are similar to nasal secretions and, thus, do not interfere with normal ciliary action. Such nasal solutions usually are isotonic and slightly buffered to a pH of 5.5 to 6.5. In addition, antimicrobial preservatives, similar to those used in ophthalmic preparations, and appropriate drug stabilizers, if required, may be included in the formulation. Various commercial nasal preparations are known and include, for example, antibiotics, steroids, antihistamines, decongestants and ipitropium bromide.

Where possible and appropriate, any of the substances delivered by devices of the present invention may optionally be in the form of liposomes or nanoparticles (e.g., nanocapsules). The formation and use of liposomes is generally known to those of skill in the art. Liposomes are formed from phospholipids dispersed in an aqueous medium such that they spontaneously form multilamellar concentric bilayer vesicles sometimes referred to as multilamellar vesicles (MLVs). MLVs are typically from 25 nm to 4 μm in diameter. When sonicated, MLVs form small unilamellar vesicles (SUVs) of about 200 to 500 angstroms in diameters having cores which contain the aqueous solution. In general, when dispersed in an aqueous medium, phospholipids can form various structures other than liposomes, depending on the molar ratio of lipid to water. At low molar lipd to water ratios, liposomes will form. The physical characteristics of liposomes depend on pH, tonicity and the presence or non-presence of divalent cations. Liposomes can interact with cells by different mechanisms, including 1) endocytosis (e.g., phagocytosis of the liposome by cells such as macrophages and neutrophils), adsorption to the cell surface, 2) interaction with cell-surface components, 3) fusion with the plasma cell membrane by insertion of the lipid bilayer of the liposome into the plasma membrane or 4) transfer of liposomal lipids to cellular or subcellular membranes, or vice versa. Varying the liposome formulation can alter which mechanism(s) by which the lyposomes will interact with cells in the paranasal sinus, nasal mucosa, etc.

A nanocapsule is any nanoparticle that consists of a shell and a space, in which desired substances may be placed. Techniques for forming nanocapsules are known in the art. Polymeric nanocapsules can be made in specific sizes and shapes. They can be produced as monodisperse particles which have precisely defined physical and chemical properties and, thus, can be tailored to facilitate release of the therapeutic or diagnostic substance in response to particular bimolecular triggering mechanisms, such as pH, mucus flow or other conditions present within the paranasal sinus or other area in the ear, nose or throat where the device is implanted. Nanocapsules can be used in the present invention as “smart drugs” which have specific chemical receptors or binding sites that will bind to specific target cells (e.g., cancer cells associated with sinus or nasal tumors or cells associated with inflammatory conditions.

It is to be appreciated that the invention has been described hereabove with reference to certain examples or embodiments of the invention but that various additions, deletions, alterations and modifications may be made to those examples and embodiments without departing from the intended spirit and scope of the invention. For example, any element or attribute of one embodiment or example may be incorporated into or used with another embodiment or example, unless otherwise specified of unless doing so would render the embodiment or example unsuitable for its intended use. Also, where the steps of a method or process have been described or listed in a particular order, the order of such steps may be changed unless otherwise specified or unless doing so would render the method or process unworkable for its intended purpose. All reasonable additions, deletions, modifications and alterations are to be considered equivalents of the described examples and embodiments and are to be included within the scope of the following claims. 

1. A method for treating a disorder of a maxillary sinus in a human or animal subject, the method comprising: forming an opening into the maxillary sinus; advancing a sinus spacer device at least partway through the opening; deploying at least one retention member of the spacer device to retain at least part of the spacer device within the maxillary sinus; introducing a substance into the spacer device to expand the device from a collapsed to an expanded configuration; and leaving the spacer device in the subject for a period of between 1 day and 60 days to allow the introduced substance to exit the spacer device and treat the disorder.
 2. A method according to claim 1, wherein forming an opening into a maxillary sinus comprises forming an opening between the nasal cavity and a maxillary sinus through a wall of the sinus.
 3. A method according to claim 2, wherein the opening is formed by inserting a penetrator through an inferior or middle nasal meatus and into the maxillary sinus.
 4. A method according to claim 3, wherein the penetrator comprises a shaft having a penetrating distal end and a curve of about 80 degrees to about 110 degrees.
 5. A method according to claim 1, wherein the opening is formed such that it enters the maxillary sinus at a downward angle.
 6. A method according to claim 1, wherein forming an opening into a maxillary sinus comprises forming an opening between the oral cavity and the maxillary sinus.
 7. A method according to claim 6, wherein the opening is formed through the canine fossa.
 8. A method according to claim 1, further comprising using an image guidance system to determine or confirm positioning of the penetrator.
 9. A method according to claim 1, wherein a penetrator that has a curve and an indicator flag for indicating the direction of the curve is used to form the opening, the method further comprising using the indicator flag to determine or confirm the direction of the penetrator curve.
 10. A method according to claim 1, wherein a penetrator having a lumen is used to form the opening, and wherein advancing the spacer device comprises: advancing a guide member through the lumen of the penetrator, through the opening and into the maxillary sinus; and advancing the spacer device over the guide member.
 11. A method according to claim 10, wherein the guide member comprises a guidewire.
 12. A method according to claim 1, wherein advancing the spacer device comprises: inserting a tubular guide into the opening; advancing the spacer device through the tubular guide; and removing the tubular guide, leaving the spacer device positioned within the opening or maxillary sinus.
 13. A method according to claim 1, wherein the spacer device comprises an elongate member having a lumen into which a stylet is receivable, and wherein advancing the spacer device comprises: inserting a stylet into the lumen of the elongate shaft; inserting the spacer device and stylet through the opening; and removing the stylet.
 14. A method according to claim 1, wherein the retention member comprises at least one projection and wherein the method further comprises: maintaining said at least one projection in a collapsed position while the at least part of the spacer device is inserted through the opening; and causing said at least one projection to transition to an extended position whereby it said at least one projection mechanically contacts at least one adjacent anatomical structure.
 15. A method according to claim 14, wherein said at least one projection comprises first and second laterally opposed projections which, when in their extended positions, span a diameter of about 14 mm to about 20 mm.
 16. A method according to claim 1, further comprising anchoring the spacer device.
 17. A method according to claim 16, wherein anchoring the spacer device comprises suturing the spacer device to tissue.
 18. A method according to claim 1, further comprising at least one of aerating the maxillary sinus and draining the maxillary sinus through a central open lumen of the spacer device.
 19. A method according to claim 1, wherein the substance comprises saline solution.
 20. A method according to claim 1, wherein the substance comprises a fluid, and wherein the fluid exits the spacer device through multiple pores on the device.
 21. A method according to claim 1, wherein the substance comprises a therapeutic agent.
 22. A method according to claim 21, wherein the therapeutic agent comprises a steroid.
 23. A method according to claim 22, wherein the steroid comprises triamcinolone.
 24. A method according to claim 23, wherein the spacer is constructed such that a dose of about 100 micrograms per day of triamcinolone will exit the spacer.
 25. A method according to claim 1, wherein the substance continues to exit the spacer device for between about 14 days and about 21 days.
 26. A method for treating a disorder of a maxillary sinus in a human or animal subject, the method comprising: dilating a maxillary sinus ostium; advancing a sinus spacer device at least partway through the maxillary sinus ostium; deploying at least one retention member of the spacer device to retain at least part of the spacer device within the maxillary sinus; introducing a substance into the spacer device to expand the device from a collapsed to an expanded configuration; and leaving the spacer device in the subject for a period of between 1 day and 60 days to allow the introduced substance to exit the spacer device and treat the disorder.
 27. A method according to claim 26 wherein the step of dilating the maxillary sinus ostium comprises dilating the maxillary sinus ostium and ethmoid infundibulum.
 28. A method according to claim 27, wherein dilating the maxillary sinus ostium and ethmoid infundibulum comprises: positioning an expandable dilator within the maxillary sinus ostium and ethmoid infundibulum; and expanding the dilator.
 29. A method according to claim 28, wherein the expandable dilator comprises a balloon, and wherein the step of expanding the dilator comprises inflating the balloon.
 30. A system useable for treating a disorder of a maxillary sinus, the system comprising: a sinus spacer device that comprises: an elongate shaft having a lumen, a proximal end and a distal end; an expandable reservoir attached to the distal end of the elongate shaft such that a substance may be introduced through the lumen of the elongate shaft into the expandable reservoir, thereby causing the reservoir to expand to a diameter of from about 3 mm to about 8 mm and a length of from about 1 mm to about 100 mm; and retention projections located proximal to the expandable reservoir, said retention projections being initially disposable in a collapsed configuration and subsequently transitionable to an expanded configuration wherein the retention projections span a diameter of from about 14 mm to about 20 mm; and a stylet having a proximal end, a distal end and an outer diameter sized to allow insertion of the stylet into the lumen of the elongate shaft.
 31. A system according to claim 30 wherein the expandable reservoir is constructed to allow a substance that has been introduced into the reservoir to exit the reservoir.
 32. A system according to claim 30 wherein the stylet is curved.
 34. A system according to claim 33 wherein the curve in the stylet is approximately 90 degrees to approximately 110 degrees.
 35. A system according to claim 30 wherein the stylet is malleable.
 36. A system for treating a disorder of a maxillary sinus, the system comprising: a sinus spacer device, comprising: an elongate shaft having a lumen, a proximal end and a distal end; an expandable reservoir attached to the distal end of the elongate shaft such that a substance may be introduced through the lumen of the elongate shaft into the expandable reservoir, thereby causing the reservoir to expand to a diameter of from about 3 mm to about 8 mm and a length of from about 1 mm to about 100 mm; and retention projections located proximal to the expandable reservoir, said retention projections being initially disposable in a collapsed configuration and subsequently transitionable to an expanded configuration wherein the retention projections span a diameter of from about 14 mm to about 20 mm; and a tubular delivery guide having a lumen through which the spacer device is insertable.
 37. A system according to claim 36 wherein the tubular delivery guide has a proximal portion and a distal portion, the distal portion being more flexible than the proximal portion.
 38. A system according to claim 36 wherein the tubular delivery guide has a proximal portion and a distal portion, the proximal portion being malleable.
 39. A system according to claim 36 wherein the tubular delivery guide has a proximal portion and a distal portion, a curve being formed in the distal portion.
 40. A system according to claim 39 wherein the curve is from approximately 80 degrees to approximately 110 degrees.
 41. A system according to claim 36 further in combination with a stylet that has a distal end, said stylet being insertable into and removeable from the lumen of the elongate shaft.
 42. A system according to claim 41 wherein the tubular delivery guide is curved and the stylet is sufficiently flexible to advance through the curve of the tubular guide. 